Abstract Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1β (IL-1β) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1β production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.
Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25-100 μg mL⁻¹) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2-ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE₂, NO, TNF-α, and IL-1β, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea is mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.
Although gastric cancer (GC) is one of the most common cancers, knowledge of its development, and carcinogenesis is limited. The present study explored the involvement of ceramide synthase 6 (CERS6) in GC carcinogenesis and prognosis. RT‐PCR, immunoblotting, and immunohistochemistry were used to examine the expression of CERS6. Transfection and small hairpin RNA technology were used to investigate the effect of CERS6 manipulation on cell proliferation and spread as well as the underlying mechanism. Moreover, xenograft proliferation was employed to explore the influence of CERS6 on tumor growth in animals. It was found that overexpression of CERS6 was significantly correlated with several clinicopathologic parameters and poor disease‐free survival. The overexpression and silencing of CERS6 in GC cells facilitated and suppressed cell proliferation and spread as well as xenograft proliferation, respectively. Mechanistic studies further revealed that CERS6 influenced cell proliferation and spread by regulating cell cycle control and metastasis‐related protein through the SOCS2/JAK2/STAT3 signaling pathway. Collectively, this study suggests that CERS6 overexpression could be a useful biomarker for predicting the outcomes of GC patients and that CERS6 targeting represents a potential modality for treating GC.
Abstract Background Dynamic somatosensory evoked potentials (DSSEP) can be used to disclose abnormalities of ascending sensory pathways at dynamic positions and diagnose cervical spondylotic myelopathy (CSM). However, radiographic tests including magnetic resonance imaging (MRI) and dynamic X-ray are used much more widely in the management of CSM. Our study aims to clarify the correlations between several radiographic parameters and the DSSEP results, and further determine their reliability with clinical data. Methods We retrospectively enrolled 38 CSM patients with surgical intervention. DSSEP tests were performed before surgery. Amplitude ratios of DSSEP N13 and N20 waves at extension and flexion were calculated and recorded as N13_E, N20_E, N13_F, N20_F, respectively. Baseline severity was evaluated with the modified Japanese Orthopedic Association (mJOA) score and the Nurick grades. Prognosis was evaluated based on the 2-year recovery rate. Sagittal diameter and transverse areas of the cord and canal were measured and the the compressive ratios at the compressed site (Compression_Ratio), central (Central_Ratio), and 1/4-lateral points (1/4-Lateral_Compression_Ratio), and spinal cord/Canal Area Ratio were calculated. The intramedullary T2 hyperintensity patterns (Ax-CCM types) were also collected from MRI axial images. Dynamic X-rays were used to test for segmental instability of the cervical spine. The correlations between radiologic findings, DSSEP data, and clinical assessments were investigated. Results We found that DSSEP N13_E and N13_F correlated with the Compression_Ratio, Central_Ratio, 1/4-Lateral_Compression_Ratio (Pearson, p < 0.05) and Ax-CCM types (ANOVA, p < 0.05) in MRI axial images and cervical segmental instability in dynamic X-ray (t-test, p < 0.05). Apart from the 1/4-Lateral_Compression_Ratio, these radiographic parameters above also correlated with the baseline clinical assessments (Spearman or ANOVA or t-test, p < 0.05) and postoperative recovery rate (Pearson or ANOVA or t-test, p < 0.05). Conclusions We found that the preoperative Compression_Ratio, Central_Ratio and 1/4-Lateral_Compression_Ratio in MRI and cervical segmental instability in dynamic X-ray could reflect the dynamic neural dysfunction of the spinal cord. Different Ax-CCM types corresponded to different DSSEP results at extension and flexion, suggesting divergent pathophysiology. These radiographic parameters could help evaluate disease severity and predict postoperative prognosis.
Study Design. Retrospective analysis. Objective. To investigate (1) whether resection of primary tumor improves survival of metastatic spinal chondrosarcoma patients and (2) which subgroups of metastatic spinal chondrosarcoma patients benefit more from primary tumor resection. Summary of Background Data. Surgical resection is the mainstay of treatment for spinal chondrosarcoma, as chondrosarcoma is inherently resistant to radiotherapy and chemotherapy. However, evidence which justifies resection of the primary tumor for patients with metastatic spinal chondrosarcoma is still lacking. Methods. We retrospectively included 110 patients with metastatic spinal chondrosarcoma in the Surveillance, Epidemiology, and End Results database from 1983 to 2016. The association between primary tumor resection and survival was evaluated using Kaplan-Meier analyses, log-rank tests, and multivariable Cox analyses. The effect of primary tumor resection on survival was further assessed in subgroups stratified by histologic subtype, tumor grade, and age. Results. Overall, 110 patients were divided into surgery group (n = 55, 50%) and nonsurgery group (n = 55, 50%). Primary tumor resection was associated with both prolonged overall survival (hazard ratio 0.262, 95% confidence interval 0.149–0.462, P < 0.001) and cancer-specific survival (hazard ratio 0.228, 95% confidence interval 0.127–0.409, P < 0.001). When we focused on surgical effects in subgroups, primary tumor resection conferred survival advantage on patients with conventional subtype, grade I to III malignancy, and an age younger than 70 years old ( P < 0.001 for overall and cancer-specific survival). However, primary tumor resection brought limited survival benefit for patients with dedifferentiated subtype and patients over 70 years old. Conclusion. The present population-based study for the first time reports a clear association between primary tumor resection and prolonged survival in metastatic spinal chondrosarcoma patients. Specifically, primary tumor resection was associated with improved survival in patients with conventional subtype, grade I to III malignancy, and an age younger than 70 years old. Level of Evidence: 4
Background: As one of the most common malignancies in the world, little is known about the molecular mechanism underlying gastric cancer (GC) and its progression. In this study, we aimed to investigate the clinical impact of the mitochondrial GTPase mitofusin 2 (MFN2) in GC. Methods: Immunohistochemistry was used to examine the expression levels of MFN2 in gastric tissues obtained from 141 patients with GC. The correlations between MFN2 protein level and clinicopathologic parameters, as well as the significance of MFN2 protein level for overall and disease-free survival were assessed. siRNA technology was used to study the effect of MFN2 knockdown on cell proliferation and invasion. Results: The overexpression of MFN2 was positively associated with depth of invasion (P = 0.0430), stage (P = 0.0325) and vascular invasion (P = 0.0077). Patients with high expression levels of MFN2 had a significantly lower overall survival rate and disease-free survival rate compared with those with low expression levels (P = 0.003 and 0.001, respectively). Multivariate Cox regression analysis showed that the overexpression of MFN2 was an independent prognostic marker for inferior overall survival and disease-free survival (P = 0.015 and 0.025, respectively). In addition, studies conducted in GC cells indicated that knockdown of MFN2 suppressed cell proliferation and invasion. Conclusions: Overexpression of MFN2 can be used as a marker to predict the outcome of patients with GC. Furthermore, targeting MFN2 might provide a new therapeutic modality for the treatment of GC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(60)'/%3e%3ccircle r='17' fill='%23000095'/%3e%3ccircle r='15' fill='%23fff'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)